Foreword

In article 1, Rohde and Lee provide the necessary background information on the prominent role of inflammation in association with traditional risk factors in the pathophysiology of atherosclerotic plaque development and rupture. Several inflammation markers, C-reactive protein (CRP) in particular, can be used to assess the risk of a first coronary event or recurrence, indicating a prominent role of inflammation at all stages of atherosclerosis, but a direct link between infections and coronary events is lacking. Several lines of clinical and experimental observations are consistent with the role of inflammation and extracellular matrix remodeling in plaque instability and rupture followed by tissue factor- dependent occlusive thrombosis of coronary arteries. Early detection of vulnerable lesions and implementation of therapies such as statins aimed at improving the integrity of the vulnerable lesion may be the foundations for a new strategy to prevent acute atherothrombotic events.

In article 2, Kathir and Adams focus on endothelial dysfunction as a predictor of acute coronary syndromes. Endothelial dysfunction is a key event and early sign of atherosclerosis, is already present in the earliest stages of acute coronary syndromes before there is any evidence of plaque formation, and is associated with vascular risk factors. Endothelial dysfunction is manifest in loss of nitric oxide (NO)-mediated vasodilatation. Oxidized low-density lipoprotein (LDL) not only reduces NO activity through various mechanisms but also promotes inflammation in the pathophysiology of plaque formation. NO-mediated endothelial dysfunction can be measured by noninvasive methods and has clinical implications. Recent studies showed a strong association between the degree of endothelial dysfunction and extent and severity of acute coronary events.

In article 3, Scirica and Morrow review the use of troponins in acute coronary syndromes (ACSs) including non-ST elevation myocardial infarction (NSTEMI) and ST elevation myocardial infarction (STEMI). Cardiac troponin has replaced creatine kinase MB but does not discriminate between ischemic and nonischemic mechanisms of myocardial injury. In combination with clinical presentation and a 12-lead electrocardiogram, troponins have proved to be an important tool for diagnosis, risk stratification, and therapeutic decision making for NSTEMI and STEMI. The appropriate clinical response to elevated levels of troponin in many other clinical settings such as renal failure, myocarditis, pulmonary embolism, and stroke remains to be defined.

In article 4, Abbate et al state that CRP should be included in the risk profile assessment and as a follow-up marker in patients after the ACS event. Fibrinogen and cytokines should not be performed in the clinical setting. The rate of event recurrence is still relatively high, 15% after an ACS. CRP at a cutoff of greater than 10 mg/L is a marker of high risk of death and at a cutoff of greater than 3 mg/L a marker of higher rate of recurrence in patients with ACS. A negative troponin level at low CRP allows a no-hospitalization or early discharge strategy. The potential cutoff levels of CRP as a population marker in preventive medicine and a marker in ACS are different. Available data recommend the use of CRP as an important prognostic marker in addition to other prognostic vascular risk factors including troponin.

In article 5, Maree and Fitzgerald delineate the proper use of aspirin and glycoprotein (GP) IIb/IIIa antagonists in patients with ACS. Plaque rupture and/ or endothelial damage and activated platelet-mediated thrombus formation on exposed extracellular matrix are central to all troponin-positive ACS. GPIIb/IIIa antagonists in addition to aspirin are not effective in acute myocardial infarction (too late because of occlusive coronary thrombosis) and troponin-negative ACS (too early because of no endothelial damage). GPIIb/IIIa antagonists in addition to aspirin are effective in patients with NSTEMI with elevated troponin or other high-risk feature and are also effective during percutaneous coronary intervention (PCI) in preventing and reducing occlusion or reocclusion of the treated coronary arteries.

In article 6, Wong and Giugliano focus on the use of low-molecular-weight heparins (LMWHs) in ACS. Meta-analyses showed superiority of LMWH to placebo and superiority of enoxaparin to unfractionated heparin (UFH) in unstable angina (UA)/NSTEMI. In-hospital LMWH is recommended for UA/NSTEMI, in particular when troponin is elevated, for short-term composite endpoints with no additional benefit beyond hospital discharge. In STEMI and during PCI, UFH is still the heparin of choice as an antithrombotic agent and has not been replaced by LMWH.

In article 7, Eikelboom and Anand nicely review the use of aspirin and clopidogrel or ticlopidine in ACS. Doses of aspirin in excess of 150 mg/day are clinically no more effective than 75 to 150 mg in patients with acute STEMI, NSTE-ACS, or during PCI. Aspirin compared with placebo prevents death after acute MI in 2.4 to 2.5% (number needed to treat: [NNT] = 40). Aspirin compared with placebo in patients with a past history of MI prevents cardiovascular events (NNT = 36). The combination of aspirin and heparin or LMWH is superior to aspirin alone in NSTE-ACS. The combination of clopidogrel plus aspirin is superior to aspirin alone in NSTE-ACS. Pretreatment with a loading dose of clopidogrel in addition to aspirin prior to PCI and continuing clopidogrel for 30 days or beyond are superior to aspirin alone. Minimizing the dose of aspirin and discontinuation of clopidogrel for 5 days for coronary artery bypass graft surgery are recommended.

In article 8, Claeys produces good evidence that a 450-mg loading dose of clopidogrel at least 6 hours prior to PCI in addition to aspirin is superior to no loading dose of clopidogrel in addition to aspirin prior to PCI. Recent data indicate that the use of GPIIb/IIIa antagonists is no longer mandatory in procedurally uncomplicated elective PCI, at least if the patients received adequate pretreatment with dual oral antiplatelet therapy of a loading dose of clopidogrel/aspirin 1 day prior to elective PCI.

In article 9, Kinlay and Ganz draw attention to the use of statins in ACS. Statins have not only an LDL cholesterol lowering effect but also multiple lipid-independent pleiotropic effects including CRP reduction. Clinical studies of statins in the secondary prevention setting document a reduction in coronary events, stroke, and death after long-term therapy. Early use of statins after MI prior to hospital discharge, in ACS with high LDL cholesterol, and in UA/NSTE-ACS resulted in a significant risk reduction in vascular mortality and morbidity. The current and future use of statins in addition to risk factor and lifestyle modifications that affect the whole vascular system should be evaluated in prospective clinical outcome studies.

In article 10, Cannon elucidates that more is needed than just guidelines to improve health care. Critical pathways in the setting of ACS are necessary to optimize evidence-based guideline recommendations, appropriate use of diagnostic tools, cardiac procedures, and therapeutic modalities to improve compliance with guidelines and to maximize the cost-effectiveness of medical care.